**20. Genetics of subacute cutaneous lupus erythematosus (SCLE)**

Subacute cutaneous lupus erythematosus represents a widespread, photosensitive, nonscarring, nonindurated form of lupus erythematosus., associated with a distinctive immunogenetic background including the production of Ro/SS-antibodies. Patients with subacute cutaneous lupus erythematosus present in most cases the HLA-A1, B8 and DR3 haplotype that is also observed in approximately 25% of the North American Caucasians; this haplotype is now referred as the 8.1 ancestral haplotype. Partial or complete deficiency in C2 and C4, whose genes are located on chromosome 6, has been reported in some patients with SCLEA single nucleotide polymorphism (SNP) in the TNF-alpha gene promoter (−308A) encoding excessive TNF-alpha expression has been associated with skin lesions in patients suffering from SCLE (the TNF, a gene is also located within the HLA region). Also, a robust association of photosensitive systemic lupus erythematosus and a complete congenital deficiency of C1q have been recently revealed. In addition, SCLE subphenotype was significantly associated with a single nucleotide polymorphism (SNP) in the second exon of the gene encoding the A chain of C1q, which is the molecule that initiates the classical pathway of complement. SCLE patients homozygous for this SNP had lower serum levels of Ciq antigen compared to SCLE patients not having this SNP. To date this C1q an SNP is the only genetic association of SCLE that lies outside the HLA region. Two recent studies are in accordance with finding that in both SCLE and CCLE IFN-pathways are increased, but CCLE does indeed express more IFN-gamma than SCLE [40, 41].
